Smith Adam C, Heo Won Do, Braun Virginie, Jiang Xiuju, Macrae Chloe, Casanova James E, Scidmore Marci A, Grinstein Sergio, Meyer Tobias, Brumell John H
Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada, M5G 1X8.
J Cell Biol. 2007 Jan 29;176(3):263-8. doi: 10.1083/jcb.200611056.
Members of the Rab guanosine triphosphatase (GTPase) family are key regulators of membrane traffic. Here we examined the association of 48 Rabs with model phagosomes containing a non-invasive mutant of Salmonella enterica serovar Typhimurium (S. Typhimurium). This mutant traffics to lysosomes and allowed us to determine which Rabs localize to a maturing phagosome. In total, 18 Rabs associated with maturing phagosomes, each with its own kinetics of association. Dominant-negative mutants of Rab23 and 35 inhibited phagosome-lysosome fusion. A large number of Rab GTPases localized to wild-type Salmonella-containing vacuoles (SCVs), which do not fuse with lysosomes. However, some Rabs (8B, 13, 23, 32, and 35) were excluded from wild-type SCVs whereas others (5A, 5B, 5C, 7A, 11A, and 11B) were enriched on this compartment. Our studies demonstrate that a complex network of Rab GTPases controls endocytic progression to lysosomes and that this is modulated by S. Typhimurium to allow its intracellular growth.
Rab鸟苷三磷酸酶（GTP酶）家族成员是膜运输的关键调节因子。在此，我们研究了48种Rab与含有鼠伤寒沙门氏菌（S. Typhimurium）非侵袭性突变体的模型吞噬体的关联。该突变体运输至溶酶体，使我们能够确定哪些Rab定位于成熟的吞噬体。总共有18种Rab与成熟的吞噬体相关联，每种都有其自身的关联动力学。Rab23和35的显性负性突变体抑制吞噬体-溶酶体融合。大量Rab GTP酶定位于野生型含沙门氏菌液泡（SCV），其不与溶酶体融合。然而，一些Rab（8B、13、23、32和35）被排除在野生型SCV之外，而其他一些（5A、5B、5C、7A、11A和11B）则在该区室中富集。我们的研究表明，Rab GTP酶的复杂网络控制内吞作用向溶酶体的进展，并且鼠伤寒沙门氏菌对其进行调节以使其在细胞内生长。
Zotero 插件